U.S. patent application number 14/906945 was filed with the patent office on 2016-06-09 for combined mri pet imaging.
The applicant listed for this patent is KONINKLIJKE PHILIPS N.V.. Invention is credited to Johan Samuel VAN DEN BRINK.
Application Number | 20160161579 14/906945 |
Document ID | / |
Family ID | 48979522 |
Filed Date | 2016-06-09 |
United States Patent
Application |
20160161579 |
Kind Code |
A1 |
VAN DEN BRINK; Johan
Samuel |
June 9, 2016 |
COMBINED MRI PET IMAGING
Abstract
Combined use is made of image values at corresponding image
locations defined by amide proton transfer MRI image data and
18F-FLT, 11C-MET, or 18F-FDG PET image data. The combined use may
include computing multimodal heterogeneity for combined PET and
amide proton transfer MRI image values, using PET image data to
distinguish different image locations during processing and/or
display of amide proton transfer image data, and tissue
classification based on combinations of values derived from the
amide proton transfer MRI and/or PET images.
Inventors: |
VAN DEN BRINK; Johan Samuel;
(Meteren, NL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KONINKLIJKE PHILIPS N.V. |
Eindhoven |
|
NL |
|
|
Family ID: |
48979522 |
Appl. No.: |
14/906945 |
Filed: |
July 23, 2014 |
PCT Filed: |
July 23, 2014 |
PCT NO: |
PCT/EP2014/065768 |
371 Date: |
January 22, 2016 |
Current U.S.
Class: |
600/411 |
Current CPC
Class: |
A61B 5/4848 20130101;
G01T 1/1603 20130101; G01R 33/481 20130101; G01R 33/5605 20130101;
G01R 33/5601 20130101 |
International
Class: |
G01R 33/48 20060101
G01R033/48; G01T 1/16 20060101 G01T001/16; A61B 5/00 20060101
A61B005/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 30, 2013 |
EP |
13178496.9 |
Claims
1. A computer program product with instructions for a programmable
image processing system that, when executed by the programmable
image processing system, will make the programmable image
processing system perform the steps of obtaining amide proton
transfer MRI image data; obtaining 18F-FLT, 11C-MET, or 18F-FDG PET
image data; making combined use of image values at corresponding
image locations defined by the amide proton transfer MRI image data
and the PET image data.
2. A computer program product according to claim 1, wherein the
instructions are configured to make the programmable image
processing system make said combined use of the image values by
evaluating a measure of multimodal heterogeneity of jointly
occurring amide proton transfer MRI and PET image values.
3. A computer program product according to claim 1, wherein the
instructions are configured to make the programmable image
processing system make said combined use of the image values in
image processing and/or image display of the amide proton image,
wherein data for image locations of the amide proton image are
processed and/or displayed distinguished based on image values
derived from the PET image at the corresponding image
locations.
4. A computer program product according to claim 3, wherein the
instructions are configured to make the programmable image
processing system assign combined classifications to image
locations and/or image areas in the amide proton transfer MRI
and/or PET image data based on joint occurrence of values derived
from the amide proton transfer MRI and PET image for the image
locations and/or image areas.
5. A computer program product according to claim 4, wherein the
instructions are configured to make the programmable image
processing system assign first classifications to the image
locations and/or image areas based on the amide proton transfer MRI
data for the data image locations and/or image areas; assign second
classifications to image locations and/or image areas based on the
PET image data for the data image locations and/or image areas;
assign a further classification based on a combination of the first
and second classifications.
6. A computer program product according to claim 3, wherein the
instructions are configured to make the programmable image
processing system select a region of interest image based on the
values of the PET image; compute a heterogeneity measure of the APT
MRI image selectively in the selected region of interest.
7. A computer program product according to claim 3, wherein the
instructions are configured to make the programmable image
processing system select the region of interest based on a received
user indication on a display screen showing the PET image and/or
based on threshold values for PET image values.
8. A PET-MRI imaging system comprising an image processing system
programmed with a computer program product according to claim
1.
9. A PET-MRI imaging system according to claim 8, comprising an
amide proton transfer MRI imaging system coupled to the image
processing system.
10. A PET-MRI imaging system according to claim 8, comprising a PET
imaging system coupled to the image processing system for providing
the 18F-FLT, 11C-MET, or 18F-FDG PET image data.
11. A PET-MRI imaging method, comprising obtaining amide proton
transfer MRI image data; obtaining 18F-FLT, 11C-MET, or 18F-FDG PET
image data; making combined use of image values at corresponding
image locations defined by the amide proton transfer MRI image data
and the PET image data.
12. A PET-MRI imaging method according to claim 11, comprising
performing respective amide proton transfer MRI scans of a subject
at stages between respective steps of a therapy of the subject;
combining images derived from the respective amide proton transfer
MRI scans each with said 18F-FLT, 11C-MET or 18F-FDG PET image.
13. A PET-MRI imaging method according to claim 11, comprising
administering a PET tracer selected from the group of 18F-FLT,
11C-MET and 18F-FDG and combinations thereof to a subject;
performing a PET scan of a sample region in the subject to form the
PET image.
Description
TECHNICAL FIELD
[0001] The invention relates to the field of PET-MRI. The invention
also relates to a computer program for MRI imaging and to an MRI
imaging system and method. The invention particularly relates to
MRI imaging for the purpose of assessing treatment response,
notably for use in treatment schemes for oncology and stroke, and
in drug discovery for medicines applicable in these treatments.
BACKGROUND OF THE INVENTION
[0002] A form of multimodal magnetic resonance imaging (MRI) and
positron emission tomography (PET) is described by Laymon et al. in
an article titled "Combined imaging biomarkers for therapy
evaluation in glioblastoma multiforme: correlating sodium MRI and
F-18 FLT PET on a voxel-wise basis", published in Magnetic
Resonance Imaging. 2012 November;30(9):1268-78.
[0003] Laymon et al. study assessment of response to cancer
therapy. Laymon et al use Na MRI images and PET images obtained
with 18F-FLT (fluorothymidine with the 18F isotope of fluor).
Laymon et al report that the two modalities may provide
complementary information regarding tumor progression and response.
In addition Laymon uses a 3T structural MRI scan as a baseline to
register the Na MRI and PET images.
[0004] Conventionally, 18F-FLT or another PET tracer such as
18F-FDG (fluorodeoxyglucose with the 18F isotope) is used for
oncologic treatment planning In proliferating cells, upregulated
DNA synthesis requires increased amounts of thymidine, which shows
up 18F-FLT in certain cell types. In addition, 18F FLT imaging
shows intra-tumour heterogeneity of proliferation in certain
tumours to correlate with predicted chemotherapeutic response (J
Nucl Med 2012; 53 (Supplement 1):387).
[0005] FDG is a glucose that accumulates in cells. Although its
version with 18F is usually detected by means of PET, Rivlin et al.
have suggested that FDG or the non-fluorinated compound 2DG
(deoxyglucose) can also be detected by means of Chemical
Exchange-dependent Saturation Transfer MRI (CEST-MRI). See
"Chemical exchange saturation transfer (CEST) MRI of 2DG and FDG as
a tool for molecular imaging of tumors and metastases" in Proc.
Intl. Soc. Mag. Reson. Med. 21 (2013) page 425.
[0006] However, the required in-vivo tracer concentrations for
detection of DG with CEST MRI may reach toxic levels. PET scans are
burdensome because they involve radioactivity. 18F-FLT and 18-FDG
used in such scans may expose patients to radiation toxicity.
Therefore it is desirable to administer only limited
quantities.
[0007] Further, the US-patent application US2009/0324035 discloses
a method to combine multiple binary cluster maps. Each cluster map
represents characteristic information, eg, from MR-BOLD, PET or
CEST MR data. Each cluster is assigned a reliability factor.
Information of the binary cluster maps is combined into a single
cluster map and a reliabilty factor is assigned to the single
cluster map.
SUMMARY OF THE INVENTION
[0008] Among others it is an object to provide a method for
improved detection, localization and characterization of cell
proliferation with PET- MRI.
[0009] A computer program product with instructions for a
programmable image processing system is provided that, when
executed by the programmable image processing system, will make the
programmable image processing system perform the steps of [0010]
obtaining amide proton transfer MRI image data; [0011] obtaining
18F-FLT, 11C-MET, or 18F-FDG PET image data; [0012] making combined
use of image values at corresponding image locations defined by the
amide proton transfer MRI image data and the PET image data. The
computer program product may comprise a machine readable medium
containing the instructions for the image processing system, such
as an optical or magnetic disk, or a semi-conductor memory, e.g. a
non-volatile semi-conductor memory. To make combined use of the
amide proton transfer MRI image data and 18F-FLT, 11C-MET, or
18F-FDG PET image data, amide proton transfer MRI and 18F-FLT,
11C-MET, or 18F-FDG PET images may be registered, i.e. a map may be
determined that map locations in the image spaces onto each other
that represent the same location in a subject.
[0013] Preferably, the combined use of image values of the amide
proton transfer (APT)-MRI image data and the PET image data is
carried-out to reconstruct a multi-modal image of which the image
data are combined in that the image values of the multi-modal image
depend on both the APT-MRI image data and the PET image data. This
multi-modal image may have image values such that the colour
rendition or the contrast rendition is dependent on image values of
each of the APT-MRI image data and the PET image data. For example
the colour or contrast rendition of e.g. the APT-MRI image is
adapted on the basis of the image values of the PET-image. In
another implementation a local heterogeneity estimate is made on
the basis of the image values of both the APT-MRI image and the
PET-image. For example the multimodal image may have vector-valued
image values, the vector at each image location in the multi-modal
image having the image values of the APT-MRI data and of the
PET-image data as its components. A multi-modal heterogeneity
estimate corresponds to evaluation of a measure of heterogeneity of
the values of this vector at locations in an image area. In yet
another implementation a heterogeneity estimate in one of the
APT-MRI data may be improved on the basis of image values, e.g. its
heterogeneity estimate of the PET-image data (or vice-versa). For
example, the heterogeneity estimate in the APT-MRI image may be
weighted locally on the basis of the image values, e.g. its local
heterogeneity estimate of the PET-image (or vice versa).
[0014] Combined use of amide proton transfer MRI image data and the
PET image data with 18F-FLT, 11C-MET, or 18F-FDG PET as PET tracers
(i.e. with the individual compounds or combinations thereof)
provides for improved detection, localization and characterization
of cell proliferation. Both amide proton transfer MRI imaging and
the PET imaging primarily sense effects related to activity within
cells. Amide proton transfer MRI imaging and the PET imaging can
provide complementary information, because they detect activity in
different metabolic pathways.
[0015] It is easy to provide an amide proton transfer MRI imaging
system that captures images at higher spatial resolution than PET
imaging. PET images with the described PET tracers are currently
considered a gold standard for treatment assessment. When a
combination of images from an amide proton transfer MRI imaging
system and a PET imaging system are used where the amide proton
transfer MRI imaging system provides information at higher spatial
resolution than the PET imaging system, the PET image can be used
to distinguish areas of interest and the amide proton transfer MRI
image data can be used to enhance spatial resolution in combination
with that distinction.
[0016] In an embodiment, data for image locations of the amide
proton transfer MRI image are processed and/or displayed
distinguished based on image values derived from the
[0017] PET image at the corresponding image locations. For example,
the amide proton transfer MRI image may displayed with different
coloring or contrast dependent on the corresponding PET image data,
or selectively only where the PET image data meets a predetermined
criterion, such as that the corresponding PET image data is within
a predetermined range, e.g. above a threshold. As another example,
when computing an image data measure from the amide proton transfer
MRI image different image locations may be weighed differently
dependent on the PET image data.
[0018] Tissue heterogeneity is an important factor for treatment
assessment. It is known that heterogeneity measures computed from
PET images for the described PET tracers can provide a useful
estimate of tissue heterogeneity. The amide proton transfer MRI
image may provide improved estimate of tissue heterogeneity because
it has higher spatial resolution. In an embodiment a measure of
multimodal heterogeneity is computed using the PET image and the
amide proton transfer MRI image values as different modes in the
multimodal heterogeneity computation. Inhomogeneity of an image of
vector image values may be computed, wherein each image location
has a vector value with a vector component dependent on the amide
proton transfer MRI image value and a vector component derive from
for the PET image representing joint occurrence of these values for
a same location. As another example, contributions of different
image regions of the amide proton transfer MRI image data to the
measure of multimodal heterogeneity may be weighed dependent on the
PET image data for those regions, for example dependent on PET
image heterogeneity.
[0019] In an embodiment, classification of image areas is based on
criteria that depend both on a value derived from the amide proton
transfer MRI and a value derived from the PET image for the image
locations and/or image areas. Thus a more elaborate classification
is possible for treatment assessment. A classification may be
defined for example by using the values derived from the amide
proton transfer MRI and PET image as respective coordinates of a
point in a virtual space, the classification depending on whether
the point lies within a region in the virtual space that has been
predefined for the class. In a further embodiment classification
may involve classifying the amide proton transfer MRI data and PET
data individually, for example dependent on whether they are in
respective value ranges defined for the class, and assign combined
classifications based on combinations of the individual
classifications. Thus for example more classes can be used, in an
image displaying local tissue classification, the classes
corresponding to different combinations of individual
classifications. As another example, a different class scope may be
defined, such as a class containing only locations with
predetermined individual classifications of the amide proton
transfer MRI image and PET image. As another example a class scope
may be defined of a class containing locations where at least one
of the amide proton transfer MRI image and PET image has a
predetermined individual classification.
[0020] In an embodiment, the PET image may be used to select a
region of interest in the amide proton transfer MRI image for use
in processing of the amide proton transfer MRI image. The image
processing system may be configured to receive a user indication of
an image location for example, and the image processing system may
be configured to select a region of image locations containing the
selected image location and further image locations that have
similar PET image data as the selected image location, e.g. PET
image data that does not differ more that a threshold amount from
the PET image data at the selected image location, or where no
image data edge is present between the selected location and the
further location. In other embodiments the image processing system
may select the region of interest without user input, for example
by selecting image locations where the image data meets a
predetermined criterion.
[0021] The computer program product may be used in an amide proton
transfer MRI imaging system for example using a PET image as input,
or in a workstation that has access to images obtained with amide
proton transfer MRI imaging and PET imaging. In an embodiment, a
combined PET-MRI scanner may be used.
[0022] The computer program product may be used in a PET-MRI
imaging method, comprising [0023] obtaining amide proton transfer
MRI image data; [0024] obtaining 18F-FLT, 11C-MET, or 18F-FDG PET
image data; [0025] making combined use of image values at
corresponding image locations defined by the amide proton transfer
MRI image data and the PET image data. For each amide proton
transfer MRI scan a corresponding PET scan may be performed, but
this may not be necessary. In an embodiment, amide proton transfer
MRI scans of a subject are performed between successive treatment
steps (e.g. radiation treatment and/or chemical treatment), and
used in combination with 18F-FLT, 11C-MET or 18F-FDG PET data
obtained at a single stage of treatment, for example before the
successive treatment steps. Combined with amide proton transfer MRI
scans from different stages, the PET image data obtained at a
single stage may be sufficient for treatment assessment. In this
way administration of PET tracers may be reduced.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] These and other objects and advantageous aspects will become
apparent from a description of exemplary embodiments, with
reference to the following figures.
[0027] FIG. 1 shows a PET-MRI imaging system
[0028] FIG. 2 shows a PET-MRI imaging arrangement
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0029] FIG. 1 shows a PET-MRI imaging system comprising PET-MRI
imaging system for forming images of a subject 10. The PET-MRI
imaging system comprises an MRI scanner 10, a PET scanner 12, an
image processing system 14 and a display screen 16. Image
processing system 14 is coupled to MRI scanner 10, PET scanner 12
and display screen 16. Image processing system 14 is configured to
combine MRI and PET images from the MRI scanner and the PET
scanner.
[0030] MRI scanner 10 is configured to perform amide proton
transfer MRI of a subject. Amide proton transfer MRI is known per
se. Amide proton transfer MRI comprises selectively saturating
amide protons by irradiating a sample area of the subject with
radio frequency (RF) electro-magnetic radiation This is followed by
conventional MRI imaging of the sample area, for example MRI
imaging of bulk water molecules, making use of the effect that
proton exchange leads to a reduced amount of excitable water
protons in the environment of the amide. Amide protons saturation
requires relatively long RF irradiation, compared to Chemical
Exchange-dependent Saturation Transfer (CEST) MRI using a special
administered CEST contrast agent.
[0031] MRI scanner 10 may comprise a conventional MRI scanner
subsystem. A conventional MRI scanner comprises one or more
gradient magnets configured to produce a magnetic field in a sample
area, an RF generator, an RF receiver, RF transmission antennas
coupled to the RF generator and RF receiver and configured to
generate and receive RF fields from the sample area, and a signal
processing system. The latter may be part of image processing
system 14. To perform amide proton transfer MRI, MRI scanner 10 may
comprise control software configured to [0032] make MRI scanner 10
generate an RF signal at a resonance frequency of amide protons,
[0033] cause MRI scanner 10 to transmit the RF signal at that
resonance frequency using a combination of RF power and duration
that is sufficient to cause saturation in the sample area and
subsequently to [0034] make MRI scanner 10 perform conventional MRI
imaging to determine (water) proton response to RF fields as a
function of position in the sample region.
[0035] Both the resonance frequency of protons in water and that of
amide protons depend on the magnetic field, but at any given
magnetic field the resonance frequency of the amide protons lies
shifted with respect to that of the water protons. The amount of
shift as a function of the magnetic field is known per se so that
the amide proton resonance frequency can be determined in advance,
but optionally the required resonance frequency may be determined
dynamically, for example by measuring water proton responses after
saturating irradiation at different frequencies in a range that
includes the amide proton resonance frequency, and selecting the RF
frequency for saturation based on those responses. The frequency
may be set at a frequency for which the responses at different
frequencies indicate maximum response.
[0036] The saturating irradiation may be applied as an RF pulse or
pulse sequence with a duration of between one to ten seconds for
example and an RF magnetic field amplitude of between one to ten
micro Tesla for example.
[0037] In a preferred embodiment differential amide proton imaging
is used. This comprises a first MRI imaging operation after
saturation by RF irradiation at the resonance frequency Fa of the
amide protons and a second MRI imaging operation after saturation
by RF irradiation tuned to a frequency Fb =2*Fw-Fa, where Fw is the
resonance frequency of protons of water. In this embodiment, the
APT-MRI image is formed by subtracting image values of images
formed by means of the first and second MRI imaging operations.
Thus contributions of non-amide protons are removed or at least
reduced. The first and second MRI imaging operations may each be
performed with the same time delay after their corresponding
saturation. Alternatively, a difference between the MRI images
obtained with and without saturation at the amide proton resonance
frequency may be used.
[0038] The MRI image difference obtained by means of saturation may
be normalized by dividing its image values by image values obtained
without preceding saturation.
[0039] FIG. 2 schematically shows a PET-MRI imaging tunnel
arrangement. A subject carrier surface 21 is symbolically shown.
The arrangement comprises a magnet coil 20, a first and second ring
shaped RF saturation coil 22a,b and a ring shaped gamma ray
detector array 26 coaxially located between first and second RF
saturation coils 22a,b. Furthermore an RF saturation signal
generator 240, a multiplexer 242, and first and second amplifiers
244 coupled between multiplexer 242 and RF saturation coils 22a,b
are shown. Multiplexer 242 is used to switch between supplying RF
saturation to saturation coils 22a,b via first and second amplifier
respectively during application of RF radiation for saturation. A
method of operating such an APT MRI imaging system is described in
co-pending European patent application no 13166255.3, which does
not include a PET detector. The coils are shown schematically.
Although the coils may be wound in a ring shape, other forms may be
used, as described in WO2011086512.
[0040] In an embodiment, the MRI scanner is equipped with a
multi-mode or multi-element volume transmit coil for RF
irradiation, and multiple RF power amplifiers that are enabled
repetitively and in an alternating fashion to improve efficiency of
the RF power amplifier performance. In the integrated PET-MRI
system, such multi-element volume transmit coils are particular
useful as they create a gap as free path from the region of
interest of the subject under investigation to the PET
detectors.
[0041] MRI scanner 10 may comprise an amplifier or amplifier system
for amplifying the tuned RF signal.
[0042] As an alternative contrast generating mechanism, electrical
properties tomography, or EPT MRI can be applied independent or
integrated with the APT MRI acquisition. This method applies signal
processing of the phase of the MR image to derive the local
conductivity (in Siemens/meter) of the region of interest.
[0043] PET scanner 12 may be implemented as a conventional PET
scanner. A conventional PET scanner comprises a gamma ray detector
system and a signal processing system. Part or all of the latter
may be part of image processing system 14.
[0044] PET scanner 12 is configured to determine gamma ray emission
intensity as a function of position in the sample region. In PET
scanning gamma ray pairs resulting from positron-electron
annihilation involving positrons emitted from a PET tracer are
detected. A
[0045] PET scanner may comprise an array of gamma ray detectors in
a ring around a subject, and a signal processing circuit coupled to
the gamma ray detectors, the signal processing circuit being
configured to detect substantially coincident gamma ray detections
from different detectors (substantially meaning temporally not more
distant than explicable by differences in travel distance a
position in the scanner to different detectors). Furthermore the
signal processing circuit of the PET scanner is configured to
determine location information from the locations of the detectors
that detected the gamma rays in the pair and/or detection
timing.
[0046] Prior to PET scanning a PET tracer is administered to the
subject. This may be done by oral ingestion for example, or
intravenously. In an embodiment .sup.18F-desoxyglucose
(.sup.18F-FLT) may be used as PET tracer. This tracer is known for
brain tumor PET studies.
[0047] Oncologic treatment planning and assessment of cancer
treatment response needs to differentiate benign and malignant
tissues at high sensitivity and specificity. Differentiation may be
based on detection of cell proliferation. Indications of cell
proliferation may be obtained using imaging biomarkers, such as 18
F FLT (fluoro-3'-deoxy-3'L-fluorothymidine). Upregulated DNA
synthesis requires increased amounts of thymidine in proliferating
cells, and 18F FLT used in the thymidine salvage pathway for DNA
synthesis is trapped upon phosphorylation by TK1 in certain cell
types. The location of cells where this occurs can be detected b
PET imaging. In addition, 18F FLT PET imaging shows intra-tumour
heterogeneity of proliferation in certain tumours to correlate with
predicted chemotherapeutic response (J Nucl Med 2012; 53
(Supplement 1):387).
[0048] It may be noted that 18F FLT is not trapped in all cell
types. See e.g. E. T. McKinley et al. Limits of [18F]-FLT PET as a
Biomarker of Proliferation in Oncology (PLOS ONE Vol 8, Issue 3,
e58938).
[0049] 18F FLT PET results in information that is complementary to
the information that is provided by APT MRI.
[0050] It is known that, among others, the APT MRI image is also
indicative of processes within cells. This may be contrasted with
conventional MRI techniques that detect mostly protons of water
outside cells, e.g. in the form of tumor associated edema or
necrosis. In contrast, APT MRI image shows locations of protein
production associated with chromosome reproduction and hence cell
replication activity.
[0051] The PET image obtained with .sup.18F-FLT is indicative of
ribosome activity. It is known that .sup.18F-FLT PET images are
also indicative of locations of cell replication activity. In other
embodiments, 11C-MET, or 18F-FDG may be used, or combinations of
two or more of 18F-FLT, 11C-MET, or 18F-FDG. Each of these is known
per se as a PET tracer. In the following 11C-MET, 18F-FDG, or
combinations thereof or with 18F-FLT may be substituted for
18F-FLT. The images obtained by MRI and PET may be three
dimensional images. In an alternative embodiment two dimensional
images may be used, e.g. of slices or projections.
[0052] For PET images it is known to use image processing to
evaluate heterogeneity of a tumor or part of a tumor. Heterogeneity
characterizes aspects of variation of the PET image values within
the tumor or part of the tumor. A number of measures of
inhomogeneity of image values of a PET image or image part that
shows a tumor or part of a tumor are known per se. For response
assessment, such inhomogeneity metrics comprise a number of
non-spatially resolved measures like Coefficient of Variation (CV),
skewness, kurtosis, or entropy of the signal intensity
distribution; as well as localized measures like the grey-level
co-occurrence matrix and its constituents e.g. dissimilarity and
homogeneity. The application of such measures is described in an
article by Willaime et al, titled "Quantification of intra-tumour
cell proliferation heterogeneity using imaging descriptors of 18F
fluorothymidine-positron emission tomography", published in Phys.
Med. Biol. 58 (2013) 187-203. Willaime et al list and evaluate a
set of alternative descriptors for use as a measure of
heterogeneity in texture analysis of a PET image (see Williame et
al table 2, incorporated by way of reference herein).
[0053] To make combined use of the amide proton transfer MRI image
data and 18F-FLT, 11C-MET, or 18F-FDG PET image data, amide proton
transfer MRI and 18F-FLT, 11C-MET, or 18F-FDG PET images may be
registered, i.e. a map may be determined that map locations in the
image spaces onto each other that represent the same location in a
subject.
[0054] MRI scanner 10 has a higher spatial resolution than PET
scanner 12. Generally it is easier to provide higher resolution
with MRI than with PET, due to the higher signal to noise ratio of
the MRI imaging data. This is also the case for APT MRI. This makes
it possible to realize a more reliable evaluation of tumor
heterogeneity using the increased spatial resolution of the APT MRI
image, while the PET heterogeneity measures are generally
compromised by partial volume effects. In an embodiment, image
processing system 14 may be configured to upsample the PET image so
as to make the number of image locations (pixels or voxels) of the
PET and APT MRI images equal, but in this case the APT MRI image
has a wider spatial frequency bandwidth of physically relevant
content than that of the PET image.
[0055] When the amide proton transfer MRI and PET images have
different sampling grids of locations in the subject, one or more
of the images may be resampled by means of interpolation to enable
a pixel to pixel or voxel to voxel registration. Alternatively, the
registration may merely define the location of pixels/voxels in one
image relative to those of the other image, enabling the
determination of an image value for a corresponding location in the
other image by interpolation, or taking the image value of a
pixel/voxel that is mapped to a region that includes the
corresponding location in the other image etc. Information derived
from image value for such corresponding locations in any such way
will be termed mutually registered image information.
[0056] Image processing system 14 may be configured to combine
mutually registered image information from the APT MRI and PET
images in one or more of a number of ways.
[0057] In a first embodiment, image processing system 14 may be
configured to use the PET image as a selector for selecting image
locations in the APT MRI image. Selection may be part of evaluation
of the APT MRI image for example, image processing system 14 using
the PET image based selection to select image locations from the
APT-MRI image that image processing system 14 will use for the
evaluation. Selection may take the form of control of display of
the APT MRI image by image processing system 14, in a way that
distinguishes image locations dependent on PET image values. For
example, image processing system 14 may display a APT MRI image
value for an image location differently (or not at all) dependent
on whether the PET image value for the image location is in a
predetermined range or not.
[0058] In a second embodiment, image processing system 14 may be
configured to use the PET image and the APT MRI image together to
select image regions. When respective predetermined image value
ranges are defined for the PET image and the APT MRI image
individually, four classes of image locations may be distinguished,
dependent on whether or not the PET image and the APT MRI image are
in the predetermined ranges. Derived types of classes include a
class wherein both the image values of an image location are in the
corresponding range and a class wherein at least one of the image
values of an image location is in the corresponding range. Other
types of classes include classes defined for respective areas in a
two dimensional plot with points that have plot coordinates derived
for the PET and APT MRI image respectively. In this case, the class
may be assigned dependent on PET and APT MRI image data according
to the location in the plot. The four mentioned classes obtained
with individual image value ranges for the PET image and the APT
MRI image correspond to rectangular areas in such a plot, but other
classes may be defined that correspond to areas of other
shapes.
[0059] Image processing system 14 may be configured to generate an
image that indicates the class of each image location. As in the
case of the first embodiment, the select image regions may be used
as part of part of evaluation of the APT MRI image and/or control
of display of the APT MRI image. Image processing system 14 may be
configured to perform combined FLT and APT classification using
predefined threshold values for high/low PET FLT and high/low
APT-MRI image values. In an exemplary embodiment, these thresholds
are a mean Standardized Uptake Value (SUV) of 2.3 for FLT PET, and
an APT MRI signal change of 3% of the water signal without
saturation transfer at a magnetic field of 3T with saturation
during 2 seconds. However, other thresholds may be used. Image
processing system 14 may provide for user controlled setting of the
thresholds.
[0060] In a third embodiment, image processing system 14 may be
configured to evaluate multimodal heterogeneity, i.e. inhomogeneity
of a multimodal PET+APT MRI image. For each image location, the PET
and APT MRI images may be considered to provide a vector of image
data, wherein the vector components are PET and APT MRI image
values for that location respectively, or combinations thereof.
Evaluation of multimodal heterogeneity corresponds to evaluation of
a measure of heterogeneity of the values of this vector at
locations in an image area.
[0061] In an embodiment, the image processing system 14 applies
histogram analysis methods as described by Willaime et al to APT
MRI data as well as to EPT MRI data to compute a measure of tumour
heterogeneity for quantification and evaluation of tumour
heterogeneity.
[0062] In another embodiment, predetermined value ranges are
defined, for example in terms of a lower threshold, or a lower and
upper threshold, and image processing system 14 is configured to
compute a volume from a count of image locations within the
predetermined range. Alternatively image processing system 14 may
compute cumulative intensity-volume histograms, with counts of
image locations with an image value equal to or higher than a lower
threshold value, as a function of the lower threshold value.
[0063] In another embodiment, image processing system 14 is
configured to compute a ratio of the cumulative intensity volumes
for two selected contrast mechanisms, like APT and EPT, or APT and
diffusion MRI ADC values, or EPT and regional perfusion blood
volume, and the like.
[0064] In another embodiment, the image processing system 14
co-registers PET and MR images, selects a region of interest and
computes a heterogeneity measure of the APT or EPT MRI image
selectively in the selected region of interest. Image processing
system 14 may configured to select the region of interest based on
user interaction and/or based on threshold values for PET image
values.
[0065] In another embodiment, image processing system 14 is
configured to apply cluster analysis to selectively generate and
display an overlay image generated from e.g. 18F FLT signal
intensities in a predefined range of values, with e.g. APT images
of a predefined set of enhancement percentages. Four images may be
generated with high FLT, high APT; low FLT, high APT; low FLT, low
APT; and high FLT, low APT. Cluster analysis may comprise a
determination whether image values are in a predetermined range.
But alternatively other known cluster analysis techniques may be
used, such as techniques based on histograms, region growing
etc.
[0066] When the APT MRI and PET images show that the APT MRI and
PET images of the tumor are correlated, this indicates that the APT
MRI image is suitable for computation of the homogeneity and
monitoring treatment response. This can be used to avoid overbroad
detection by APT MRI. Image processing system 14 computes a measure
of homogeneity of image values of the APT MRI image or part thereof
from MRI scanner 10. Because the measure of homogeneity of image is
based on an APT MRI image from MRI scanner 10 with higher spatial
resolution than the PET image from PET scanner 12, a more reliable
value of the measure of homogeneity is made possible, which makes
more different measures of homogeneity suitable for treatment
assessment than in the case of PET images alone.
[0067] In an embodiment, image processing system 14 may be
configured to compute the measure of homogeneity for a plurality of
blocks of APT-MRI image locations, and image processing system 14
may be configured to form and display a heterogeneity image
representing values of the measure of homogeneity at different
locations.
[0068] In an embodiment, image processing system 14 may be
configured to use location dependent data, such as intensity,
derived from the PET image to modulate display of the heterogeneity
image from the APT-MRI image as a function of location in the
image. For example, in an embodiment, image processing system 14
may be configured to compare the location dependent data derived
from the PET image with a threshold value and to perform modulation
by enabling or disabling display of the heterogeneity image at
image locations corresponding to the locations associated with the
data from the PET image, dependent on the comparison. Other forms
of modulation may include more graded amplitude modulation
dependent on the data from the PET image.
[0069] In an embodiment, image processing system 14 may be
configured to compute a further measure of homogeneity from the PET
image, e.g. a plurality of such values for respective blocks, and
image processing system 14 may be configured to display a combined
image with image values based on combinations of the values of the
measure heterogeneity for the PET and APT-MRI images. Image
processing system 14 may be configured to upscale the resolution of
the image with values of the measure of heterogeneity obtained from
the PET image, for example by interpolation, to the resolution of
the image with values of the measure of heterogeneity obtained from
the APT-MRI image and combine the values for corresponding
locations in these images to form the combined image.
[0070] In an embodiment image processing system 14 is configured to
compute values of measures of heterogeneity for corresponding
regions from the APT MRI image and the PET image. In embodiment
image processing system 14 is configured to generate and display a
plot of the values of the measures of heterogeneity of the PET
image values versus those of the APT-MRI image values. Image
processing system 14 may be configured to display further plots
wherein values of the measure of heterogeneity of the PET image
values or the APT-MRI image values are plotted versus values of a
measure of heterogeneity of MRI contrast like diffusion ADC, FA,
kurtosis, spectroscopy choline levels
[0071] When and/or where the APT-MRI image exhibits correlation
with the .sup.18F-FLT PET image, this ensures that the tumor is of
a type that can be detected by APT-MRI. In this case, assessment
can be performed using the APT-MRI images, without the burden of
additional .sup.18F-FLT PET scans after respective treatment steps.
In an embodiment, image processing system 14 is configured to apply
heterogeneity computations to the MRI images from MRI scanner
10.
[0072] In an embodiment .sup.18F-FLT PET is used to form a PET
image at a first stage prior to a treatment step and APT MRI is
used to form an APT-MRI at this stage prior to the treatment step
and a further APT-MRI image after that treatment step, or a
plurality of APT-MRI images each after a respective treatment step
in a succession of treatment steps. Herein the treatment steps may
be radiotherapy and/or chemotherapy steps. The first stage may be a
stage prior to all treatment steps of a therapy, or it may be an
intermediate stage between successive treatment steps.
[0073] In an embodiment, image processing system 14 is configured
to derive values of the texture analysis metrics for APT MRI, or
combined metrics based on PET image intensity based MRI analysis
pre- and post-treatment and to plot as these values in a parametric
response map. In such a map, the per-image location pre-treatment
values (from image locations that may be voxels or pixels) are
plotted on the x-axis and the per-image location post-treatment
values on the y-axis. Values that are far from the orthogonal axis
indicate image locations with large changes of its value. Based on
this change criterion for one of the contrasts, like APT MRI or EPT
MRI, image processing system 14 may perform texture analysis or
volume fraction analysis for the other contrasts, e.g. the 18F FLT
values, at the image locations with changed parameter values, and
at the image locations that do not show signal changes. Such
analysis selectively shows cell proliferation from e.g. 18F FLT in
the voxels that respond or do not respond.
[0074] When the APT-MRI image obtained at the first stage exhibits
correlation with the .sup.18F-FLT PET image, this ensures that the
tumor is of a type that can be detected by APT-MRI. In this case,
assessment can be performed using the APT-MRI images, without the
burden of additional .sup.18F-FLT PET scans after respective
treatment steps.
[0075] In an embodiment PET scanner 12 may be separate from MRI
scanner 10. In this embodiment PET scanner 12 may be configured to
transmit .sup.18F-FLT PET image data to image processing system 14
for use in processing the APT MRI images.
[0076] In another embodiment, a combined APT MRI/PET system is
used, comprising MRI/PET scanners that are both capable of
performing measurements while the subject is in the same position
in a scanner. Designs of combined PET-MRI scanners that enable such
measurements are known per se. More preferably APT MRI/PET system
is used, that is capable of performing PET and MRI measurements
substantially simultaneously. This facilitates registration of the
PET and MRI images. Alternatively, an MRI/PET system is used PET
and MRI scans of a subject are performed when the subject is at
respective different positions. In this case, image processing
system 14 may be configured to register the PET and MRI images
prior to their combination.
[0077] In an embodiment, image processing system 14 is configured
to combine registered MRI and PET images from MRI scanner 10 and
PET scanner 12. Any one of a range of combination methods may be
used. For example, image processing system 14 may be configured to
detect locations in the APT-MRI and/or PET images of the sample
region at which the APT-MRI and PET signals exceed respective
threshold values and form a combine image with image values that
that single out locations where this is the case. Image processing
system 14 may cause the combined image to be displayed on display
screen 16. In a further embodiment image processing system 14 may
use the combined image to evaluate properties within image areas by
weighing measured properties for image location according to
whether the APT-MRI and/or PET signals exceed respective values. In
other embodiments the APT-MRI and PET signals may be combined in
other ways, for example by controlling the luminance channel of
each image location of the combined image dependent on the APT-MRI
signal for that image location and controlling the color saturation
channel dependent on the PET signal for that image location, or any
other way of combining the signals at the image location. In
another embodiment, image processing system 14 may be configured to
compute a difference image between the PET image and the APT-MRI
image and display an image representing this difference.
[0078] Instead of combining individual APT-MRI images with a PET
image, difference images between APT-MRI images may be combined
with the PET image. Although the application of image processing
operations for evaluating heterogeneity to APT-MRI has been shown
in combination with use of PET image information, it should be
appreciated that application of such image processing operations to
APT-MRI may also yield useful information when not combined with
use of PET image information.
[0079] According to another aspect, EPT MRI imaging may be used
instead of the described use of APT-MRI or in combination APT-MRI
to form combined APT-EPT MRI images for use instead of the
described use of APT-MRI.
[0080] Other variations to the disclosed embodiments can be
understood and effected by those skilled in the art in practicing
the claimed invention, from a study of the drawings, the
disclosure, and the appended claims. In the claims, the word
"comprising" does not exclude other elements or steps, and the
indefinite article "a" or "an" does not exclude a plurality. A
single processor or other unit may fulfill the functions of several
items recited in the claims. The mere fact that certain measures
are recited in mutually different dependent claims does not
indicate that a combination of these measured cannot be used to
advantage. A computer program may be stored/distributed on a
suitable medium, such as an optical storage medium or a solid-state
medium supplied together with or as part of other hardware, but may
also be distributed in other forms, such as via the Internet or
other wired or wireless telecommunication systems. Any reference
signs in the claims should not be construed as limiting the
scope.
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